Epigenetically Upregulated MicroRNA-602 Is Involved in a Negative Feedback Loop with FOXK2 in Esophageal Squamous...

MicroRNA is an endogenous, small RNA controlling multiple target genes and playing roles in various tumorigenesis processes. In this study, our results revealed that miR-602 expression levels in tumor tissues and preoperative serum from esophageal squamous cell carcinoma (ESCC) patients were higher than those in non-tumorous tissues and healthy volunteers. miR-602 overexpression was closely related to lymph node metastasis and TNM stages and correlated short overall, and it acted as an independent prognostic marker of ESCC. The methylation status of the miR-602 gene indicated more frequent hypomethylation of the CpG sites located upstream of the miR-602 gene in the ESCC tissues than in the adjacent normal tissues, and the methylation status of miR-602 correlated inversely with its expression levels. Subsequently, miR-602 overexpression promoted ESCC proliferation and metastasis and regulated cell cycles in vitro and in vivo. Mechanistically, a dual-luciferase experiment validated that Fork head box (FOX)K2 (FOXK2) was a direct target of miR-602. More importantly, systemic delivery of formulated miR-602 antagomir could reduce tumor growth and increased FOXK2 protein expression in nude mice. This work provides novel insight into the molecular pathogenesis of ESCC.